Adult neurogenesis, mental health, and mental illness: hope or hype?

Abstract

Psychiatric and neurologic disorders take an enormous toll on society. Alleviating the devastating symptoms and consequences of neuropsychiatric disorders such as addiction, depression, epilepsy, and schizophrenia is a main force driving clinical and basic researchers alike. By elucidating these disease neuromechanisms, researchers hope to better define treatments and preventive therapies. Research suggests that regulation of adult hippocampal neurogenesis represents a promising approach to treating and perhaps preventing mental illness. Here we appraise the role of adult hippocampal neurogenesis in major psychiatric and neurologic disorders within the essential framework of recent progress made in understanding "normal" adult neurogenesis. Topics addressed include the following: the life cycle of an adult hippocampal stem cell and the implications for aging; links between learning and hippocampal neurogenesis; the reciprocal relationship between cocaine self-administration and adult hippocampal neurogenesis; the role of adult neurogenesis in an animal model of depression and response to antidepressant exposure; the impact of neonatal seizures on dentate gyrus neurogenesis; and the contribution of a schizophrenia-susceptibility gene to adult hippocampal neurogenesis. These topics are discussed in light of the regulation of adult neurogenesis, the relationship to normal neurogenesis in adulthood and aging, and, importantly, the manipulation of neurogenesis to promote mental health and treat mental illness.

Figure 1.

Stages of adult hippocampal neurogenesis. A, The SGZ straddles the border of the hippocampal dentate gyrus granule cell layer (GCL) and hilus. The neurogenic SGZ contains cells at various stages of neurogenesis, which are individually shown in B. C, Cells in discrete stages of maturation are differentially influenced by pharmacological and physiological stimuli. This list is not meant to be comprehensive but rather highlight stimuli discussed in this review. Figure by Jessica L. Ables.